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Conformational Ensemble of Disordered Proteins Probed by Solvent Paramagnetic Relaxation Enhancement (sPRE)
Author(s) -
Kooshapur Hamed,
Schwieters Charles D.,
Tjandra Nico
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201807365
Subject(s) - intrinsically disordered proteins , residual dipolar coupling , chemical physics , protein folding , small angle x ray scattering , relaxation (psychology) , paramagnetism , folding (dsp implementation) , chemistry , protein structure , macromolecule , conformational ensembles , molecular dynamics , crystallography , nuclear magnetic resonance spectroscopy , scattering , computational chemistry , physics , biology , condensed matter physics , biochemistry , stereochemistry , electrical engineering , engineering , neuroscience , optics
Abstract Characterization of the conformational ensemble of disordered proteins is highly important for understanding protein folding and aggregation mechanisms, but remains a computational and experimental challenge owing to the dynamic nature of these proteins. New observables that can provide unique insights into transient residual structures in disordered proteins are needed. Here using denatured ubiquitin as a model system, NMR solvent paramagnetic relaxation enhancement (sPRE) measurements provide an accurate and highly sensitive probe for detecting low populations of residual structure in a disordered protein. Furthermore, a new ensemble calculation approach based on sPRE restraints in conjunction with residual dipolar couplings (RDCs) and small‐angle X‐ray scattering (SAXS) is used to define the conformational ensemble of disordered proteins at atomic resolution. The approach presented should be applicable to a wide range of dynamic macromolecules.